Metallic implant which is degradable in vivo

ABSTRACT

The invention relates to a medical implant made of a metallic material. After fulfilling its temporary support function, the implant is degraded by corrosion at a predetermined rate. Negative long-term effects are thus avoided.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to implants made of metallic materials foruse in the human or animal body.

2. Description of Related Art

Implants of this type have in principle been known for a long time. Thefirst implants were developed for orthopaedic purposes, for examplescrews and nails for fixing bone fractures. These initially consisted ofrelatively simple iron alloys which were prone to corrosion under invivo conditions. The corrosion led to metals being released as ions inthe direct vicinity of the bone providing an unwanted stimulus for thegrowth of bone tissue. The bone grew more than is actually wanted andnecessary. This led to damage to healthy bone material.

For this reason, attempts have been made to fabricate metallic implantsin principle from materials with maximum corrosion resistance. Currentlyin use in this connection are mainly corrosion-resistant stainlesssteels, tantalum and titanium. These implants persist as foreign bodiesafter the implantation and they are recognized as such by the body. Theycan be removed only by a second operation.

In addition, metallic implants are known in the specialty of vascularsurgery and cardiology, angiology and radiology. These implantscomprise, for example, endoluminal and vessel supports (stents) fortreating lesions. These supports are used, for example, for widening andmaintaining the lumen of narrowed vessels by keeping the vessel lumen atan appropriately optimal internal diameter using a balloon catheter(balloon expandable) or self-expanding from the vessel lumen outwards.The implant is intrinsically necessary only until the diseased vessel isable permanently to maintain the necessary diameter under its own powerdue to biological repair processes. This is generally the case about 4weeks after implantation.

However, some disadvantages are associated with permanent retention of ametallic implant. As a foreign body, the implant leads to local andpossibly also systemic reactions. In addition, the self-regulation ofthe affected vessel segment is impeded. The continual (pulsatile) stresson the metal may lead to fatigue fractures, which in the case oflarge-lumen implants (e.g. occlusion systems such as umbrellas) may leadto new medical problems. About 20% of vessel supports in smaller lumina(2.5-6 mm) cause renewed stenosis (called in-stent stenosis) which,given the large number of implants, accumulates to an additional medicaland economic burden. In some vessel regions (e.g. extracranial vessels,leg arteries) the metallic structure may be permanently deformed byforces acting from outside, resulting in renewed vessel obstruction orinduced vessel occlusion. Every permanent implant is additionallyassociated with problems in particular for younger patients becauseretention for decades is unavoidable.

The only completely biodegradable implants disclosed to date, forexample in DE 2502884 C2, are made of synthetic materials. There isdisclosure therein of coating an orthopaedic implant withpolymethylmethacrylate which is biodegradable. Other synthetic materialscomprise polylactide and polyglycolic esters. In addition, EP 0006544 B1discloses a biodegradable ceramic material based on calcium phosphate,which is likewise used for coating metallic implants.

Finally, WO 81/02668 discloses an orthopaedic implant which comprises acorrosion-resistant metallic basic component and a biodegradableintermediate metallic layer for the bone contact region. Thisintermediate layer forms together with the basic component anelectrochemical cell and generates an electrical voltage which promotesbone growth. At the same time, the surface layer which may, for example,consist of silver alloys is degraded. This leads to the desired effect,that bone growth is beneficially influenced for as long as necessary andthen, after complete degradation of the surface coating, the electricalstimulus declines.

Previously disclosed biodegradable polymer-based substances are used invascular surgery. Their mechanical properties on the one hand and thesubsequent foreign-body reaction during the biodegradation on the otherhand lead to them being unsuitable on their own as material forimplantation. Metallic materials/alloys have favourable mechanicalproperties (elasticity, deformability, stability) while being lessbulky, which is an important precondition for administration throughthin-lumen guide systems in the transcutaneous procedure.

SUMMARY OF THE INVENTION

It is therefore an object of the present invention to provide implantsmade of biodegradable material having at the same time advantageousmechanical properties.

This object is achieved by a medical implant made of metallic material,characterized in that the material is degradable in vivo throughcorrosion.

Because the medical implant is fabricated from a metallic material whichis degradable in vivo through corrosion, in the first place themechanical advantages of metallic materials are present. The corrosivedegradation of the implant within a time scale which can be set by thechoice of material prevents, on the other hand, the adverse long-termeffects of the metallic foreign body occurring. It is moreoverbiologically advantageous if the material is pure iron, whereappropriate with a content of up to 7% carbon or an alloy or a sinteredmetal, the main constituent of which is selected from the group ofalkali metals, of alkaline earth metals, iron, zinc or aluminium.Magnesium or iron is currently preferred as main constituent.

The biological, mechanical and chemical properties of the materials canbe beneficially affected if a subsidiary constituent is provided in theform of manganese, cobalt, nickel, chromium, copper, cadmium, lead, tin,thorium, zirconium, silver, gold, palladium, platinum, rhenium, silicon,calcium, lithium, aluminium, zinc, iron, carbon or sulphur. The materialpreferred overall at present is either an alloy of magnesium with acontent of up to 40% lithium plus addition of iron, or an iron alloywith a small content of aluminium, magnesium, nickel and/or zinc.Corrosion which is particularly satisfactory at the start of thedegradation period is afforded by an alloy or a sintered metal made ofapproximately equal parts of zinc and iron.

Advantageous decomposition times have furthermore been afforded bymaterials with magnesium as main constituent and either

-   -   0-40% lithium, 0-5% iron and less than 5% other metals or rare        earths;    -   2-5% aluminium, 0-12% lithium and 1-4% rare earths, in        particular cerium, lanthanum, neodymium and/or praseodymium,    -   6-12% lithium, 2% aluminium and 1% rare earths,    -   0-8% lithium, 2-4% aluminium and 1-2% rare earths,    -   8.5-9.5% aluminium, 0.15%-0.4% manganese, 0.45-0.9% zinc    -   4.5-5.3% aluminium, 0.28%-0.5% manganese or    -   30-40% lithium and 0-5% other metals and/or rare earths.

Magnesium alloys of these types are available, for example, under thenames AZ91D, AM50A and AE42.

The design of the medical implant has several basic variants. The basiccomponent provided for a vessel support is a tubular structure withadditional processing. Advantageous occlusion systems (e.g. ductusarteriosus, congenital and acquired septal defects, arteriovenous shuntconnections) are passively and/or actively unfoldable umbrella forms,helices or complex components. The invention is also applicable tooccluders as systems for occluding connections between cavities, vesselsor duct systems.

It is additionally advantageous to provide the implant as fastening orsupporting device for temporarily fixing tissue parts in the form ofimplants or transplants.

To adjust the rate of corrosion of the material, it is advantageous ifthe thickness of the material is chosen as a function of the compositionof the materials so that the degradation or corrosion process in vivo isessentially complete in between 5 days and 6 months, in particularbetween 2 weeks and 8 weeks.

This results in the fixing device which is no longer necessarydisappearing after the tissue implant has taken.

Finally, it is advantageous if the implant is designed as orthopaedicimplant, as implant for dentistry, for surgery to the upper abdomen orfor accident surgery, in particular for treating the human body, inwhich case the alloy must be chosen so that bone growth is not adverselyor excessively influenced. Orthopaedic implants according to theinvention in the form of nails, screws or plates can be designed todegrade after the treated bone fracture has set and not require removalin a second operation.

Various exemplary embodiments of the present invention are indicatedbelow.

EXAMPLE 1 Vessel Support

A stent according to the invention is fabricated from a tubular basiccomponent of the metallic material and subsequent processing. Themechanical structure of stents of this type is known, for example, fromEP 0221570 B1, in which case the material is, however, acorrosion-resistant stainless steel.

In this example of the stent according to the invention, the material iseither an alloy having magnesium as main constituent and, whereappropriate, the subsidiary constituents lithium, iron, zinc and tracesof nickel, or an alloy having iron as main constituent and thesubsidiary constituents chromium and nickel plus, where appropriate,traces of other additions. The percentage composition of the magnesiumalloy should be approximately in the region of 50-98% magnesium, 0-40%lithium, 0-5% iron and less than 5% other metals, and that of the ironalloy approximately in the region of 88-99% iron, 0.5-7% chromium and0.5-3.5% nickel plus less than 5% other metals. The wall thickness ofthe stent struts should be between 50 and 100 mm after the processing.

In practice, the stent according to the invention will be inserted in amanner known per se using a balloon catheter into a pathologicallynarrowed blood vessel and there dilated or released as self-expandingstent, in which case it keeps the blood vessel at the required diameter.A restenosis remaining without stent implantation (recoil) and/or atissue tear induced by the dilatation are effectively treated. Within2-4 weeks the stent is covered by intimal tissue and initially retainsits supporting function. The blood vessel acquires a new intrinsicstability through tissue growth as a result of its own repair processesin the region of the implanted stent. The vessel lumen is stabilized atan optimal level. The choice of the alloy material together with thechosen wall thickness result, on the other hand, in the stent graduallybeing degraded in the wall of the blood vessel and being present only intraces after 4-12 weeks. The disadvantages of a permanent implant whichare decreased or eliminated by the present invention. Such disadvantagesinclude local and possibly systemic reactions, impedence of theself-regulation of the affected vessel segment, stress on the metal dueto pulsations leading to fatigue fractures and, in the case oflarge-lumen implants including occlusion systems such as umbrellas, maylead to new medical problems.

EXAMPLE 2 Occlusion System

An occlusion system (umbrella) according to the invention is fabricatedfrom a metallic skeleton to which a plastic umbrella is affixed.Umbrellas of this type are known, for example made of the alloy MP35N orNitinol. Occlusion systems of this type are used to occlude defects insepta of the heart. The wall thickness of the metallic framework isabout 500 mm. In practice, the umbrella is folded up in a manner knownper se and released in the defect which is to be occluded. Within 3-4weeks, the umbrella is covered by endogenous tissue and acquires a newintrinsic stability thorough this tissue growth. The choice of the alloymaterial together with the tissue wall thickness results in the metallicframework being degraded within 4 weeks to a few months and beingpresent only in traces after one year. The plastic content of theumbrella remains, which is not critical because of the flexibility ofthe material. The degradation of the metallic portion has the advantageby comparison with known umbrellas that, even if there are unpredictedstresses, e.g. associated with traffic accidents, there is no longer arisk of vessel walls being pierced. Moreover the advantage according tothe invention is achieved even if the degradation results initially inmechanical instability of the framework.

EXAMPLE 3 Helix for Occluding Vessels (Occluder)

A helix (coil) according to the invention is fabricated from a metallicmaterial wound helically, and the helix is prefixed. The diameter of theinitial winding is 0.1-1 mm depending on the vessel to be occluded.Helices (coils) of this type are known, for example made of Nitinol,platinum alloys or tungsten alloys.

In the present embodiment according to the invention, the material is analloy with iron as main constituent and with subsidiary constituentsnickel and/or chromium and traces of magnesium and zinc.

In practice, the occluding helix (coil) is inserted in the extendedstate in a cardiac catheter in a manner known per se and is advancedthrough the latter as far as the vessel to be occluded. When the helixis released from the cardiac catheter it resumes its previous shape andoccludes, through its lumen and its thrombogenicity, which can beincreased by Dacron or other fibres, the vessel to be occluded. Afterthe vessel has thrombosed and connective tissue has grown in, theocclusion mechanism acquires a new intrinsic stability. The administeredhelix is gradually degraded so that only traces of the implantedmaterial are still present after about one year.

The exemplary embodiments mentioned above can be fabricated both withuse of magnesium alloys and with use of iron alloys. The materials arenot known to have toxic effects at the concentrations to be expected.

Magnesium alloys have the advantage that it is possible to select veryaccurately the degradation rate to be expected in vivo by a suitablechoice of the other alloy constituents. In addition, magnesium isphysiologically very well tolerated. Iron alloys are advantageous interms of the mechanical stability, which is manifested by the small wallthicknesses possible for the implants. The alloy material can thereforebe selected depending on the case for which it is used.

In one aspect, the present invention provides medical implants which aremade of a metallic material, characterized in that the material isdegradable in vivo through corrosion. Metallic materials from whichimplants of the invention can be made are characterized in that theprimary material is pure iron or an alloy whose main constituent isselected from the group comprising the following: alkali metals,alkaline earth metals, iron, zinc, aluminium. In a further aspect, theprimary metallic material from which implants of the invention can bemade is further characterized in that the material contains magnesium,iron or zinc as main constituent. In one preferred embodiment, a medicalimplant according to the invention is characterized in that the metallicmaterial contains iron and 0.5 to 7% carbon. In another aspect, amedical implant according to the invention is characterized in that themetallic material contains iron and zinc in approximately the sameconcentration.

In an additional aspect, a medical implant according to the invention ischaracterized in that the metallic material contains as subsidiaryconstituents one or more elements from the group comprising thefollowing: Mn, Co, Ni, Cr, Cu, Cd, Pb, Sn, Th, Zr, Ag, Au, Pd, Pt, Re,Si, Ca, Li, Al, Zn, Fe, C, S. In some preferred embodiments, themetallic material contains 50-98% magnesium, 0-40% lithium, 0-5% ironand less than 5% other metals or rare earths. In other preferredembodiments, the metallic material contains 79-97% magnesium, 2-5%aluminium, 0-12% lithium and 1-4% rare earths, in particular cerium,lanthanum, neodymium and/or praseodymium. In yet other preferredembodiments, the alloy is characterized in that the material contains85-91% magnesium, 6-12% lithium, 2% aluminium and 1% rare earths. In yetother embodiments, the metallic material contains 86-97% magnesium, 0-8%lithium, 2%-4% aluminium and 1-2% rare earths.

In additional preferred embodiments, the metallic material contains8.5-9.5% aluminium, 0.15%-0.4% manganese, 0.45-0.9% zinc and theremainder to 100% magnesium. In still other preferred embodiments, themetallic material of a medical implant according to the invention ischaracterized in that the material contains 4.5-5.3% aluminium,0.28%-0.5% manganese and the remainder to 100% magnesium. In additionalpreferred embodiments, the metallic material is characterized in thatthe material contains 55-65% magnesium, 30-40% lithium and 0-5% othermetals and/or rare earths. In yet additional preferred embodiments, themetallic material is characterized in that the material contains88-99.8% iron, 0.1-7% chromium and 0-3.5% nickel plus less than 5% othermetals or the material contains 90-96% iron, 3-6% chromium and 0-3%nickel plus 0-5% other metals.

In another key aspect, a medical implant according to the presentinvention is characterized in that the implant is a vessel supporthaving an essentially tubular basic component. Preferred shapes for animplant of the invention include a helix (coil), an umbrella, a stent, awire network, a clip or a plug. In an additional key aspect, a medicalimplant according to the present invention is characterized in that theimplant has an endoluminal supporting function in hollow organs and/orduct systems (e.g. ureters, bile ducts, urethra, uterus, bronchi). Inanother significant aspect, a medical implant according to the presentinvention is characterized in that the implant is an occluder useful ina system for occluding connections between cavities, vessels or ductsystems, or the implant is a fastening or supporting device fortemporarily fixing tissue implants or transplants. In still othersignificant embodiments, a medical implant of the invention includes anorthopaedic implant, for example, a screw, a nail, a wire, a plate or apart of a joint.

As a further advantage, a medical implant according to the presentinvention includes those where the thickness of the material is chosenas a function of the composition of the material so that the degradationor corrosion process in vivo is essentially complete within the timeperiod, or region, of 5 days up to 6 months, in particular between 2weeks and 8 weeks. As another advantageous aspect, the thickness of thematerial is chosen as a function of the composition of the material sothat the degradation or corrosion process in vivo is essentiallycomplete within the region of 6 months up to 10 years, in particularbetween 1 year and 5 years. Preferably, the metallic materialcomposition, thickness and other dimensions, are chosen so that thedegradation or corrosion process in vivo initially leads to mechanicalinstability of the implant shape before the degradation process of themetallic material is essentially complete.

1. A vessel support or stent for widening and maintaining the lumen ofnarrowed vessels, said vessel support or stent being made from ametallic material degradable in vivo through corrosion, wherein thevessel support or stent has a substantially hollow tubular base body andis self expandable, and wherein the material is an alloy, the mainconstituent of which is magnesium.
 2. The vessel support or stentaccording to claim 1, wherein the material contains 79-97% of magnesium,2-5% of aluminium, 0-12% of lithium and 1-4% of rare earths.
 3. Thevessel support or stent according to claim 2, wherein the rare earthsare selected from the group consisting of cerium, lanthanum, neodymiumand praseodymium.
 4. The vessel support or stent according to claim 1,wherein the material contains 85-91% of magnesium, 2% of aluminium,6-12% of lithium and 1% of rare earths.
 5. The vessel support or stentaccording to claim 1, wherein the material contains 86-97% of magnesium,2-4% of aluminium, 0-8% of lithium and 1-2% of rare earths.
 6. Thevessel support or stent according to claim 1, wherein the materialcontains 8.5-9.5% of aluminium, 0.15-0.4% of manganese, 0.45-0.9% ofzinc and the remainder to 100% magnesium.
 7. The vessel support or stentaccording to claim 1, wherein the material contains 4.5-5.3% ofaluminium, 0.28-0.5% of manganese and the remainder to 100% magnesium.8. The vessel support or stent according to claim 1, wherein thematerial contains 55-65% of magnesium, 30-40% of lithium and 0-5% ofother metals and/or rare earths.
 9. The vessel support or stentaccording to claim 1, wherein the thickness of the material is chosen independence on the composition of the material such that the process ofdegradation or corrosion in vivo is substantially completed in the rangefrom 5 days up to 6 months after implantation.
 10. The vessel support orstent according to claim 1, wherein the thickness of the material ischosen in dependence on the composition of the material such that theprocess of degradation or corrosion in vivo is substantially completedin the range from 6 months up to 10 years after implantation.
 11. Thevessel support or stent according to claim 1, wherein the materialcontains, as secondary constituent, one or more elements from the groupconsisting of: Mn, Co, Ni, Cr, Cu, Pb, Sn, Th, Zr, Ag, Au, Pd, Pt, Re,Si, Ca, Li, Al, Zn, Fe, C, S.
 12. The vessel support or stent accordingto claim 1, wherein the thickness of the material is betweenapproximately 50 μm and approximately 100 μm.
 13. The vessel support orstent according to claim 1, wherein the thickness of the material ischosen in dependence on the composition of the material such that thedegradation or corrosion process in vivo is substantially completedbetween 2 weeks and 8 weeks after implantation.
 14. The vessel supportor stent according to claim 1, wherein the thickness of the material ischosen in dependence on the composition of the material such that theprocess of degradation or corrosion in vivo is substantially completedbetween 1 year and 5 years after implantation.
 15. The vessel support orstent according to claim 1, wherein the material contains approximately50-89% magnesium, 0-40% lithium, 0-5% iron, and less than 5% othermetals or rare earths.
 16. A vessel support or stent for widening andmaintaining the lumen of narrowed vessels, said vessel support or stentbeing made from a metallic material degradable in vivo throughcorrosion, wherein the vessel support or stent has a substantiallyhollow tubular base body, wherein the material contains 8.5-9.5% ofaluminium, 0.15-0.4% of manganese, 0.45-0.9% of zinc and the remainderto 100% magnesium.
 17. A vessel support or stent for widening andmaintaining the lumen of narrowed vessels, said vessel support or stentbeing made from a metallic material degradable in vivo throughcorrosion, wherein the vessel support or stent has a substantiallyhollow tubular base body, and wherein the material is an alloycontaining 4.5-5.3% of aluminium, 0.28-0.5% of manganese and theremainder to 100% magnesium.
 18. A vessel support or stent for wideningand maintaining the lumen of narrowed vessels, said vessel support orstent being made from a metallic material degradable in vivo throughcorrosion, wherein the vessel support or stent has a substantiallyhollow tubular base body, and wherein the material is an alloycontaining 55-65% of magnesium, 30-40% of lithium and 0-5% of othermetals and/or rare earths.
 19. A vessel support or stent for wideningand maintaining the lumen of narrowed vessels, said vessel support orstent being made from a metallic material degradable in vivo throughcorrosion, wherein the vessel support or stent is a balloon expandablestent having a substantially hollow tubular base body, and wherein thematerial is an alloy, the main constituent of which is magnesium.